Pyrrolo[2,3-D]pyrimidine compounds

Abstract

Described herein are pyrrolo[2,3-d]pyrimidine compounds, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing these compounds, and methods for their preparation.

1. A compound of Formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; wherein: 
         R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; and 
         when R 1  is hydrogen, then R 2  is selected from the group consisting of (C 5 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 5 -C 6 )alkyl, (C 1 -C 6 )alkenyl, halo(C 1 -C 6 )alkenyl, phenyl, phenyl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, heterocyclyl, and heterocyclyl(C 1 -C 6 )alkyl; 
         when R 1  is (C 1 -C 6 )alkyl, then R 2  is selected from the group consisting of (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, phenyl, phenyl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, heterocyclyl, and heterocyclyl(C 1 -C 6 )alkyl; 
         wherein (C 3 -C 6 )cycloalkyl, wherever it occurs, is optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; and 
       
       wherein when R 1  is hydrogen and R 2  is cyclobutyl, then the cyclobutyl is substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino;
 wherein phenyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, hydroxy, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, cyano(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, aminosulfonyl, and (C 1 -C 6 )alkylaminosulfonyl; 
 wherein heterocyclyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, and (C 1 -C 6 )alkylamino; and 
 wherein the (C 1 -C 6 )alkyl in phenyl(C 1 -C 6 )alkyl and heterocyclyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       2. The compound of  claim 1 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; and 
 when R 1  is hydrogen, then R 2  is selected from the group consisting of (C 5 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 5 -C 6 )alkyl, halo(C 1 -C 6 )alkenyl, phenyl, phenyl(C 1 -C 6 )alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, indolyl, indazolyl, pyridinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, indolylmethyl, pyridinylmethyl, pyrimidinylmethyl, pyrazinylmethyl, pyrazolylmethyl, tetrahydrofuranylmethyl, and pyridinylethyl; and 
 when R 1  is (C 1 -C 6 )alkyl, then R 2  is selected from the group consisting of (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, phenyl, phenyl(C 1 -C 6 )alkyl, pyrazinylmethyl, and pyridinylmethyl; 
 wherein cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, wherever they occur, are optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, phenyl(C 1 -C 6 )alkyl, and (C r  C 6 )alkoxycarbonylamino; and wherein when R 1  is hydrogen and R 2  is cyclobutyl, then the cyclobutyl is substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; 
 wherein phenyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, hydroxy, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, cyano(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and aminosulfonyl; 
 wherein indolyl, indazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, and tetrahydrofuranyl, wherever they occur, are optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and amino; and 
 wherein the (C 1 -C 6 )alkyl in phenyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       3. The compound of  claim 1 , wherein
 R 1  is hydrogen; 
 R 2  is selected from the group consisting of (C 5 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 5 -C 6 )alkyl, (C 1 -C 6 )alkenyl, and halo(C 1 -C 6 )alkenyl; 
 wherein the (C 3 -C 6 )cycloalkyl in (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C r  C 6 )alkoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       4. The compound of  claim 3 , wherein
 R 1  is hydrogen; 
 R 2  is selected from the group consisting of (C 5 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 5 -C 6 )alkyl, (C 1 -C 6 )alkenyl, and halo(C 1 -C 6 )alkenyl; wherein the (C 3 -C 6 )cycloalkyl in (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       5. The compound of  claim 4 , wherein
 R 1  is hydrogen; 
 R 2  is selected from the group consisting of cyclopropylmethyl and trifluorobutenyl; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       6. The compound of  claim 1 , wherein
 R 1  is (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkenyl, and halo(C 1 -C 6 )alkenyl; 
 wherein the (C 3 -C 6 )cycloalkyl in (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       7. The compound of  claim 6 , wherein
 R 1  is (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, and hydroxy(C 1 -C 6 )alkyl; 
 wherein the (C 3 -C 6 )cycloalkyl in (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl is optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       8. The compound of  claim 6 , wherein
 R 1  is (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of (C 1 -C 6 )alkyl and hydroxy(C 1 -C 6 )alkyl; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       9. The compound of  claim 6 , wherein
 R 1  is methyl; 
 R 2  is selected from the group consisting of methyl and hydroxyethyl; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       10. The compound of  claim 1 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; and 
 R 2  is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; 
 wherein cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl are optionally substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; and 
 wherein when R 1  is hydrogen and R 2  is cyclobutyl, then the cyclobutyl is substituted with one or more substituents selected from the group consisting of hydroxy(C 1 -C 6 )alkyl, phenyl, halophenyl, phenyl(C 1 -C 6 )alkyl, and (C 1 -C 6 )alkoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       11. The compound of  claim 10 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; and 
 R 2  is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; 
 wherein cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl are optionally substituted with one or more substituents selected from the group consisting of hydroxypropyl, phenyl, fluorophenyl, phenylmethyl and tert-butoxycarbonylamino; and 
 wherein when R 1  is hydrogen and R 2  is cyclobutyl, then the cyclobutyl is substituted with one or more substituents selected from the group consisting of hydroxypropyl, phenyl, fluorophenyl, phenylmethyl and tert-butoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       12. The compound of  claim 11 , wherein R 1  is hydrogen. 
     
     
       13. The compound of  claim 11 , wherein R 1  is (C 1 -C 6 )alkyl. 
     
     
       14. The compound of  claim 11 , wherein
 R 1  is selected from the group consisting of hydrogen and methyl; and 
 R 2  is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; 
 wherein cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl are optionally substituted with one or more substituents selected from the group consisting of hydroxypropyl, phenyl, fluorophenyl, phenylmethyl and tert-butoxycarbonylamino; and 
 wherein when R 1  is hydrogen and R 2  is cyclobutyl, then the cyclobutyl is substituted with one or more substituents selected from the group consisting of hydroxypropyl, phenyl, fluorophenyl, phenylmethyl and tert-butoxycarbonylamino; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       15. The compound of  claim 11 , wherein
 R 1  is hydrogen; 
 R 2  is selected from the group consisting of cyclopropyl, fluorophenylcyclopentyl, hydroxypropylcyclohexyl, and tert-butoxycarbonylaminocyclobutyl; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       16. The compound of  claim 1 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of phenyl, phenyl(C 1 -C 6 )alkyl, heterocyclyl, and heterocyclyl(C 1 -C 6 )alkyl; and 
 wherein phenyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, hydroxy, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, cyano(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and aminosulfonyl; 
 wherein heterocyclyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and amino; and 
 wherein the (C 1 -C 6 )alkyl in phenyl(C 1 -C 6 )alkyl and heterocyclyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       17. The compound of  claim 16 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of phenyl and phenyl(C 1 -C 6 )alkyl; and 
 wherein phenyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, hydroxy, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, cyano(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and aminosulfonyl; and 
 wherein the (C 1 -C 6 )alkyl in phenyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       18. The compound of  claim 17 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of phenyl and phenyl(C 1 -C 4 )alkyl; 
 wherein phenyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of cyano, chloro, fluoro, hydroxy, methyl, trifluoromethyl, cyanomethyl, methoxy, and aminosulfonyl; and 
 wherein the (C 1 -C 4 )alkyl in phenyl(C 1 -C 4 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of fluoro and hydroxy; and 
 R 3  is selected from the group consisting of hydrogen and methyl. 
 
     
     
       19. The compound of  claim 18 , wherein
 R 1  is selected from the group consisting of hydrogen and methyl; 
 R 2  is selected from the group consisting of phenyl and phenyl(C 1 -C 4 )alkyl; 
 wherein phenyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of cyano, chloro, fluoro, hydroxy, methyl, trifluoromethyl, cyanomethyl, methoxy, and aminosulfonyl; and 
 wherein the (C 1 -C 4 )alkyl in phenyl(C 1 -C 4 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of fluoro and hydroxy; and 
 R 3  is selected from the group consisting of hydrogen and methyl. 
 
     
     
       20. The compound of  claim 16 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of heterocyclyl and heterocyclyl(C 1 -C 6 )alkyl; and 
 wherein heterocyclyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and amino; and 
 wherein the (C 1 -C 6 )alkyl in heterocyclyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       21. The compound of  claim 20 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of 3-12 membered ring heterocyclyl and 3-12 membered ring heterocyclyl(C 1 -C 6 )alkyl; and 
 wherein heterocyclyl, wherever it occurs, is optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and amino; and 
 wherein the (C 1 -C 6 )alkyl in heterocyclyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       22. The compound of  claim 21 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of indolyl, indazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, tetrahydrofuranyl, indolyl(C 1 -C 6 )alkyl, indazolyl(C 1 -C 6 )alkyl, pyridinyl(C 1 -C 6 )alkyl, pyrimidinyl(C 1 -C 6 )alkyl, pyrazinyl(C 1 -C 6 )alkyl, pyrazolyl(C 1 -C 6 )alkyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl(C 1 -C 6 )alkyl, and tetrahydrofuranyl(C 1 -C 6 )alkyl; and 
 wherein indolyl, indazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, tetrahydrofuranyl are optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and amino; and 
 wherein the (C 1 -C 6 )alkyl in indolyl(C 1 -C 6 )alkyl, indazolyl(C 1 -C 6 )alkyl, pyridinyl(C 1 -C 6 )alkyl, pyrimidinyl(C 1 -C 6 )alkyl, pyrazinyl(C 1 -C 6 )alkyl, pyrazolyl(C 1 -C 6 )alkyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl(C 1 -C 6 )alkyl, and tetrahydrofuranyl(C 1 -C 6 )alkyl is optionally substituted with one more substituents independently selected from the group consisting of halo and hydroxy; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       23. The compound of  claim 21 , wherein
 R 1  is selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 2  is selected from the group consisting of indolyl, indazolyl, pyridinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, indolylmethyl, pyridinylmethyl, pyrimidinylmethyl, pyrazinylmethyl, pyrazolylmethyl, tetrahydrofuranylmethyl, and pyridinylethyl; and 
 wherein indolyl, indazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, and tetrahydrofuranyl are optionally substituted with one or more substituents independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and amino; and 
 R 3  selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl. 
 
     
     
       24. The compound of  claim 23 , wherein
 R 1  is selected from the group consisting of hydrogen and methyl; 
 R 2  is selected from the group consisting of indolyl, indazolyl, pyridinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, indolylmethyl, pyridinylmethyl, pyrimidinylmethyl, pyrazinylmethyl, pyrazolylmethyl, tetrahydrofuranylmethyl, and pyridinylethyl; 
 wherein indolyl, indazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, and tetrahydrofuranyl, are optionally substituted with one or more substituents independently selected from the group consisting of chloro, methyl, methoxy, and amino; and 
 R 3  selected from the group consisting of hydrogen and methyl. 
 
     
     
       25. The compound of  claim 1 , wherein the compound is selected from the group consisting of:
 N-(cyclopropylmethyl)-1-{cis-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-(3,4,4-trifluorobut-3-en-1-yl)methanesulfonamide; 
 N-(2-hydroxyethyl)-N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[(6-aminopyridin-2-yl)methyl]-N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-(pyridin-3-ylmethyl)methanesulfonamide; 
 N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-(pyrazin-2-ylmethyl)methanesulfonamide; 
 N,N-dimethyl((1r,4r)-4-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclohexyl)methanesulfonamide; 
 N-cyclopropyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[trans-4-(1-hydroxy-1-methylethyl)cyclohexyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 tert-butyl (3-{[({trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methyl)sulfonyl]amino}cyclobutyl)carbamate; 
 N-[(1R,2R)-2-(4-fluorophenyl)cyclopentyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-(1-benzylcyclobutyl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-[(1S,2R)-2-phenylcyclopropyl]methanesulfonamide; 
 -(2-{[({trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methyl)sulfonyl]amino}ethyl)benzenesulfonamide; 
 N-[2-(4-hydroxyphenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-(2,4-dimethylphenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-(2-methoxyphenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-(2,2-difluoro-2-phenylethyl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-(4-methylphenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-fluoro-2-(4-fluorophenyl)propyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-fluoro-2-(3-fluorophenyl)propyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-(3-methoxyphenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 N-[2-fluoro-2-(4-fluorophenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-{2-[4-(trifluoromethyl)phenyl]ethyl}methanesulfonamide; 
 N-{2-[2-fluoro-4-(trifluoromethyl)phenyl]ethyl}-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}rnethanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-(2-phenylethyl)methanesulfonamide; 
 N-benzyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(4-methoxybenzyl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[4-(cyanomethyl)phenyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(4-cyanophenyl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(4-chlorophenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(2-fluorophenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(3-fluorophenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(3-chlorophenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(2-fluoro-4-isopropylphenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(3,4-difluorophenyl)-2-hydroxyethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[3-(2-methoxyphenyl)propyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[2-(3,4-dichlorophenyl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 1-{cis-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-(2-phenylethyl)methanesulfonamide; 
 N-benzyl-1-{cis-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(4-methoxybenzyl)-1-{cis-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-(pyridin-3-ylmethyl)methanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-1H-pyrazol-5-ylmethanesulfonamide; 
 N-(5-methyl-1H-pyrazol-3-yl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-1H-indol-5-yl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(6-chloropyridin-3-yl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-1H-indazol-5-yl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(6-methoxypyridin-3-yl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-(6-methylpyridin-3-yl)-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[(2-methyl-1H-indol-5-yl)methyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[(5-methylpyrazin-2-yl)methyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}-N-[(2R)-tetrahydrofuran-2-ylmethyl]methanesulfonamide; 
 N-[2-(6-methylpyridin-2-yl)ethyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; 
 N-[(4,6-dimethylpyrimidin-2-yl)methyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; and 
 N-[(1,3-dimethyl-1H-pyrazol-4-yl)methyl]-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}methanesulfonamide; or 
 a pharmaceutically acceptable salt thereof. 
 
     
     
       26. A pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof.